Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Syndrome

Pain

Somatoform Disorders

Mental Disorders

Psychotic Disorders

Quality of Life

Not applicable. No intervention will be done. it is an observational study assessing pain after mastectomy and the quality of life as assessed from validated questionnaires given to the patients at regular intervals

Non interventional study

APARNA S CHATTERJEE, MD,FCARCSI

Breast cancer is the most common cancer in women in India and accounts for 27% of all cancers in women. Incidence rises in early thirties, peaks at 50-64 years. Approximately 48% are below 50 years of age. Most present when symptoms develop, so are 2B and beyond. Treatment depends on the stage of the disease. Surgical removal of the tumour is part of the treatment attempting a cure.

Simple mastectomy involves removal of breast tissue without axillary lymph node dissection or removal of chest wall muscles. Radical mastectomy involves removal of the entire breast, skin, pectoralis major and minor muscles and ipsilateral axillary lymph nodes. Modified radical mastectomy involves removal of the breast and ipsilateral axillary lymph nodes. The pectoralis muscle is preserved. Breast conserving surgery involves removal of tumour with or without axillary dissection. The extent of surgery tells us about the nerve damage, local tissue handling. For example operating in upper and outer quadrant of breast and axilla increases nerve handling in that particular region. Local radiation also plays a role.

Persistent pain after mastectomy was first reported in the 1970s by Wood and defined by International Association for Study of Pain (IASP) as pain in the anterior aspect of the thorax, axilla, and/or upper half of the arm beginning after mastectomy or quadrantectomy and persisting for more than three months after surgery and known as Postmastectomy pain Syndrome (PMPS). It is a common problem, with a 25- 60% incidence. The pain is described as burning or tenderness with paroxysms of lancinating, shock-like pain, and also described by some as dysesthesia (perception of non noxious stimuli as painful). Risk factors for PMPS include age, raised Body mass index (BMI), severity of postoperative pain, type of surgery, susceptibility to pain with a history of other pains such as headache and dysmenorrhoea. Axillary hematoma and postoperative radiotherapy have also been implicated in the development of PMPS.

Tata Memorial Hospital, is a tertiary cancer institute in India. Around 4000 patients with suspected breast cancers register annually at the hospital and approximately 2800 breast cancer surgeries are performed yearly. Very few studies on PMPS in Indian population exist. We therefore plan to identify the incidence of PMPS in our patients and also the severity of pain along with its impact on daily function and quality of life

Tata Memorial Hospital, a 629 bed tertiary cancer institute conducts approximately 6000 surgeries per year. Approximately 4000 (4239 in 2015) patients with suspected breast cancers register annually at the hospital and around 2800 breast cancer surgeries are performed every year. Very few studies on PMPS in Indian population exist. The investigators therefore, aim to identify the incidence of post mastectomy pain syndrome PMPS) in this population. The investigators also aim to identify the severity of postmastectomy pain along with its impact on daily function and quality of life.

STUDY DESIGN:

Prospective study over 12 months with follow up until 6th month from enrollment with interim analysis in the month of November for presentation of the CoPI's thesis.

MATERIALS \& METHODS:

Prospective study over a period of 12 months from commencement of study after Institutional ethics committee approval, at Tata Memorial hospital and ACTREC. Female patients scheduled for undergoing surgery for breast cancer conservative and radical and willing to participate will be enrolled in the study after obtaining a written informed consent. Pain scores will be assessed using Numerical rating scale \[with pain score 1-3 mild, 4 to 6 moderate and 7 and above severe\]. History of predisposition to recurrent headaches and dysmenorrhea will be noted. Details of disease stage, chemotherapy and/or radiotherapy will also be documented from the Electronic medical records. Analgesia will be managed by the primary surgical team as is currently being done. The analgesia administered to the patient will also be recorded. participants noted to have moderate to severe pain despite analgesics prescribed by the surgical team will be referred to the acute pain service (APS) for further management.

Postoperative pain severity both the average \& worst pain will be recorded at discharge from hospital, 1st, 4th and 6th month after the surgery. The Details of postoperative pain analgesic use and effect on daily function will be documented with the help of postal cards with questionaires in envelop addressed to the investigators. Study will emphasize on the type, severity, the site of pain whether, lateral or anterior chest wall, axilla, ipsilateral medial upper arm or back, the type of pain (burning, tingling, shooting, stabbing etc) and effects on daily function and quality of life. Details of postoperative hematoma, infection, local recurrence will also be recorded from the history, electronic medical records and documents of participants. Details of postoperative chemotherapy and radiation will also be obtained from patient's notes and the electronic medical record All participants will be administered the short form of the Brief Pain inventory \[BPI\], EORTC QLQ 30, preoperatively, at 1 month, 4 months \& 6 months after surgery.

The Brief pain inventory {BPI} (obtained with permission from MD Anderson), which assesses the severity of pain and impact of pain on daily functions will be administered to the participant in the language familiar to them, preoperatively, at 1 month, 4th and 6th month postoperatively. The short form comprises of nine questions related to the severity of pain, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week.It has been widely used and validated in several languages the world over.

EORTC QLQ \[Quality of life Questionaries \] is an integrated system for assessing quality of life \[health related \]. This self administered questionnaires incorporates five functional scales, physical \[PF\], role \[RF\], cognitive \[CF\], emotional \[ef\], and social; three symptoms scale for fatigue, pain and nausea/vomiting; a global health quality of life scale and several single items for financial impact and additional symptoms like diarrhea, appetite loss, sleep disturbance. This would help identify the quality of life of the participants and its affection.

If a participant cannot follow up at the said intervals, the pain scores would be obtained telephonically and the BPI, EORTC QLQ 30 form in prepaid envelopes would be given to them at discharge which they would have to duly fill in and post them to the given address at the appropriate intervals. If the next follow up to the hospital coincides with the 4th or 6th postoperative month, the participant will visit the pain clinic for an assessment and completing the BPI.

Postmastectomy Pain Syndrome in an Indian Cancer Hospital

Post Mastectomy Pain Syndrome at an Indian Tertiary Cancer Centre: Incidence, Pain Severity, Impact on Daily Function and Quality of Life

presence of pain around the mastectomy site and ipsilateral arm after the mastectomy

How severe the pain is after mastectomy from the Pain intensity obtained from the Brief Pain inventory questionnaire

How severe the pain is after mastectomy from the pain intensity obtained from the Brief Pain inventory questionnaire

How the pain after mastectomy per se affects day to day functioning of the patient and how the quality of her life is affected. The impact of pain on daily life will be identified from the Brief Pain inventory questionnaire which the patient would have to complete at this time point.

The impact of the mastectomy on Quality of life of the patient would be assessed from the EORTC-QLQ 30 questionnaire completed by the patient

How the pain per se affects day to day functioning of the patient.The impact of pain on daily life will be identified from the Brief Pain inventory questionnaire which the patient would have to complete at this time point.

The impact of the mastectomy on the quality of life of the patient would be assessed from the EORTC-QLQ 30 questionnaire completed by the patient at his time point.

How the pain per se affects day to day functioning of the patient .The impact of pain on daily life will be identified from the Brief Pain inventory questionnaire which the patient would have to complete at this time point.

the impact of teh mastectomy on the quality of life of the patient would be assessed from the EORTC-QLQ 30 questionnaire completed by the patient at this time point.

Tata Memorial Centre

Professor

Musculoskeletal Diseases

Nervous System Diseases

Mobility Limitation

Shoulder Pain

Arthralgia

Joint Diseases

Neurologic Manifestations

This group includes 15 patients who received muscle energy technique post-surgery in addition to traditional shoulder exercise, 3 sessions/week for four weeks.

This group includes 15 patients who received mobilization in addition to traditional shoulder exercise, 3 sessions/week for four weeks.

It was applied on the shoulder flexion and the external rotation. An isometric contraction of the agonist muscle (the muscle which requires stretching) for 7 seconds with gentle muscle contraction to avoid the risk of increasing the muscle tone. This contraction started just short of the restrictive barrier. After that, the patient is asked to relax for 2-3 seconds and then the therapist stretches the contracted muscle in the opposite direction for 30 seconds. This is repeated three repetitions for each muscle.

Muscle energy technique

At the start of each session, the physical therapist examined the patient's ROM in all directions to obtain information about the end-range position and the end feel of the glenohumeral joint. Start with rhythmic mid-range mobilization with the patient in a supine position. The therapist's hands are placed close to the glenohumeral joint, and the humerus is brought into a position of maximal flexion in the sagittal plane. After 10 to 15 repetitions of intensive mobilization techniques in this end-range position, the direction of mobilization will be altered by varying the plane of elevation or by varying the degree of rotation. When alternating the direction of mobilization, other movements such as gliding techniques and distraction in that joint position were (inferior gliding, anterior gliding, and posterior gliding).

Maitland mobilization

Traditional shoulder exercises in the form of shoulder range of motion exercises, stretching exercises and, scapular stabilization.

Traditional shoulder exercise

Shaimaa MA El Sayeh, PhD

The purpose of this study was to investigate the effect of muscle energy technique versus Maitland's mobilization on shoulder pain and disability after neck dissection surgeries.

Thirty patients with shoulder pain and limited ROM post-neck dissection surgeries participated in this study. Patients were subdivided into two groups, fifteen patients in each group. Group A received the muscle energy technique and group B received Maitland's mobilization.

Data obtained from both groups regarding the Visual Analogue Scale, it has a 100-mm-long horizontal line labeled ''no pain' (with or without related facial expressions) at one extreme and ''worst pain ever' at the other. Pain intensity is determined by the length of the line as measured from the left-hand side to the point marked, The Shoulder Pain and Disability Index, it has two subscales; The pain subscale includes five questions about pain intensity. The disability subscale includes eight questions about difficulty in different orders. Each question of both pain and disability subscale was scaled in numeric ratings ranging from 0 to 10. Each score was summed up and transformed into percentages. Finally, the average score between pain and disability subscale comprised the total SPADI scores ranging from 0 (the best) to 100 (the worst), and shoulder flexion, abduction, and external ROM were statistically analyzed and compared.

Patients were subdivided into two groups, fifteen patients in each group. Group A received the muscle energy technique and group B received Maitland's mobilization.

Muscle Energy Technique Versus Maitland Mobilization on Shoulder Pain and Disability

Muscle Energy Technique Versus Maitland Mobilization on Shoulder Pain and Disability After Neck Dissection Surgeries.

A Visual Analogue Scale (VAS) is one of the pain rating scales used for the first time in 1921 by Hayes and Patterson. It is often used in epidemiology and clinical research to measure the intensity or frequency of various symptoms. It has a 100-mm-long horizontal line labeled ''no pain' (with or without related facial expressions) at one extreme and ''worst pain ever' at the other. Pain intensity is determined by the length of the line as measured from the left-hand side to the point marked.

It is a self-reported questionnaire consisting of 13 items divided in two parts: pain and disability sub-scale. The pain subscale includes five questions about pain intensity. The disability subscale includes eight questions about difficulty in different orders. Each question of both pain and disability subscale was scaled in numeric ratings ranging from 0 to 10. Each score was summed up and transformed into percentages. Finally, the average score between pain and disability subscale comprised the total SPADI scores ranging from 0 (the best) to 100 (the worst).

Through using the universal goniometer to measure the shoulder flexion, abduction and, external rotation.

Cairo University

Lecturer of Physical Therapy

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Breast Neoplasms

Peripheral Nervous System Diseases

Acute Pain

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Docetaxel

Etoricoxib

Taxane

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Prophylactic etoricoxib (60 mg) was administered orally at each course of docetaxel-containing chemotherapy, which started from the day of chemotherapy and was performed once per day for 8 days (day 1-8).

Kun Wang, MD

A phase II randomized clinical trial was conducted to determine whether etoricoxib could prevent or ameliorate the incidence and/or severity of docetaxel-induced acute pain syndrome. We also aimed to determine if there are any improvement of the late-onset peripheral neuropathy as well as quality of life with prophylactic etoricoxib for breast cancer patients who receive docetaxel chemotherapy.

Docetaxel plays a key role in reducing the recurrence of early-stage breast cancer as well as improving survival outcomes of advanced breast cancer patients, but it causes a variety of adverse events, including myalgia and arthralgia, peripheral neuropathy, febrile neutropenia, and hypersensitivity reactions and so on. The myalgia and arthralgia induced by docetaxel, which have been together referred to as taxane-associated acute pain syndrome (T-APS), were reported to occur in 3.6% to 70% of patients, and the symptoms usually occurred 24-48 hours after docetaxel infusion and lasted for 3-5 days. Previous studies found that patients who experienced myalgia and arthralgia due to docetaxel administration were more likely to have chronic peripheral neuropathy, which supported that T-APS could be a form of neurologic toxicity. T-APS may significantly influence patients' sleep and daily life, and even caused discontinuation of chemotherapy. Therefore, it is clinically meaningful to explore some prophylactic drugs for the T-APS. Previous studies had used glutamine, corticosteroids, Shakuyaku-Kanzo-To (a Japanese herb), and gabapentin to prevent paclitaxel-induced myalgia and arthralgia, but failed to provide enough evidence for clinical practice. Etoricoxib, a selective COX-2 inhibitor, is a nonsteroidal anti-inflammatory drug (NSAID) that has showed comparable efficacy in acute and chronic pain, with fewer gastrointestinal (GI) adverse events compared with traditional NSAIDs. Therefore, we conducted a phase II randomized clinical trial to investigate whether etoricoxib could prevent or ameliorate the incidence and/or severity of docetaxel-induced acute pain syndrome. We also aimed to determine if there are any improvement of the late-onset peripheral neuropathy as well as quality of life with prophylactic etoricoxib for breast cancer patients who receive docetaxel chemotherapy.

Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib

Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib for Breast Cancer Patients: A Phase II Randomized Trial

Total incidence of myalgia and arthralgia of patients across all cycles of docetaxel chemotherapy

Incidence of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy

Severity of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy; the severity of pain was evaluated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).

Duration of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy; the duration of pain was counted by days.

incidence of severe myalgia and arthralgia (score, defined as greater than 5 on a scale from 0 to 10) of patients during the period of docetaxel chemotherapy by cycle and across all cycles

Functional Assessment of Cancer Therapy-Breast（FACT-B）subscale during the period of docetaxel chemotherapy was assessed; the scores range from 0 to 144, higher scores mean a better outcome (higher quality of life)

Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale (FACT-Ntx score \<44), Eastern Cooperative Oncology Group neuropathy scale (ENS) subscale and EMG were performed at 3 months after the completion of chemotherapy.

Assessment of adverse events was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale.

Guangdong Provincial People's Hospital

Pain, Postoperative

Chronic Pain

Mastodynia

Soft Tissue Neoplasms

Breast Diseases

Skin Diseases

Postoperative Complications

Chronic Graft Versus Host Disease

Central Nervous System Depressants

Antiemetics

Gastrointestinal Agents

Anesthetics

Dexamethasone

Ropivacaine

Dexamethasone acetate

Pecs block under real-time ultrasound guidance after anesthesia induction will be performed. In specific, using the in-plane insertion technique, after visualization of the entire needle as a bright hyperechoic line and aiming between pectoralis major and pectoralis minor at the 3rd rib level, 2 ml of normal saline 09% will be injected first, to verify the correct position of the needle. Followingly, 10 mL ropivacaine 0.5% will be injected in order to block the lateral and medial pectoral nerves. Finally, another 15 ml of ropivacaine 0.5% plus 4 mg of dexamethasone will be injected between the pectoralis minor muscle and the anterior serratus muscle,at the level of the 4th and 5th ribs, after negative aspiration, to block the intercostal and intercostobrachial nerves. Using the color Doppler the vessels will be identified, so that their puncture is avoided during the procedures.

Pecs block under real-time ultrasound guidance after anesthesia induction will be performed.

Pecs block

no regional block will be performed in this arm

no Pecs block

Kassiani Theodoraki

The aim of the present study is to investigate the incidence of chronic pain following breast cancer surgery in Cyprus, discover its associated risk factors and explore the impact of Pecs Blocks on the appearance of post mastectomy chronic pain symptoms

Breast cancer is the commonest type of malignancy in women. Chronic postoperative neuropathic pain may appear either in the early postoperative period or at a later stage, usually 3-6 months post-operatively. Chronic post-operative pain syndrome of any magnitude usually involves 19-57% of patients that have undergone any kind of surgical procedure, while 5% of them experience intense symptoms. Risk factors for developing post-mastectomy pain syndrome include younger age, increased Body mass Index (BMI), psychological profile, co-existence of other painful conditions, pre-operative radiotherapy/chemotherapy, type of surgical procedure and anaesthesia, persistent acute postoperative pain, etc. Consequently, chronic post mastectomy pain syndrome results in significant psychosomatic sequelae with variable social impacts for the female patients.

The aim of the present study will be to investigate the incidence of chronic pain following breast cancer surgery in Cyprus, discover its associated risk factors and explore the impact of Pecs Blocks on the appearance of post mastectomy chronic pain symptoms.

During the preoperative visit, the women will be informed about the study and will be instructed to the use of the pain numeric rating scale (NRS) graded from 0 to 10. Standardized anesthesia will be administered. All patients will receive 1000 mg of paracetamol and 0.07 mg/ Kg of morphine intraoperatively. In the Post-Anesthesia Care Unit (PACU), patients will receive additional morphine boluses on request, until NRS score is lesser or equal than 4. Postoperative nausea and vomiting will be treated with ondansetron 4 mg iv. After discharge from PACU, patients will receive a combination of paracetamol 1 gr/6h and im pethidine 75 mg on request, as per hospital protocol.

Numerical rating scores (NRS) at rest and movement will be measured at 6h, 12h and 24h postoperatively. Additionally, the time to first request for analgesia after surgery will be noted.

All patients will also be evaluated 3 and 6 months after surgery with the use of NRS at rest and movement and additionally, via the use of Douleur Neuropathique (DN4) questionnaire for the occurence of neuropathic pain.

The Impact of Pecs Blocks on Postmastectomy Pain Syndrome

The Impact of Pecs Blocks on the Appearance of Post Mastectomy Chronic Pain Symptoms

pain score by the use of Numeric Rating Scale (NRS) 6 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"

pain score by the use of Numeric Rating Scale (NRS) 12 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"

pain score by the use of Numeric Rating Scale (NRS) 24 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"

occurrence of chronic pain at the site of the operation 3 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement

occurrence of chronic pain at the site of the operation 6 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement

time of first request for analgesia after the operation

additional analgesic consumption in the first 24 hours after the operation

satisfaction from postoperative analgesia on a four-point Likert scale with 1 marked as minimal satisfaction and 4 as maximal satisfaction

Pecs block-related complications at the site of the local anesthetic injection

Aretaieion University Hospital

Professor of Anesthesiology

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Cancer Pain

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Pancrelipase

Pancreatin

All participants get the same device treatment with the Scrambler Therapy device, up to 10 treatments.

Superficial neuromodulation using EKG type electrodes \[Scrambler (MC5-A Calmare) Therapy\]

Scrambler Therapy Device

Thomas J Smith, MD

Pain is the predominant and most feared symptom of pancreas cancer, and is often incompletely relieved. Scrambler Therapy is a new way of treating pain by providing "non-pain" information to confuse the nervous system and reset the damaged nerve pathways. It has been useful in treating many types of pain, but has not been adequately tested in the pain associated with pancreas cancer. The goal of this study is to evaluate the effect of Scrambler Therapy on typical abdominal pain associated with pancreas cancer. The investigators hypothesize that pain scores from day 0 (pre) to day 28 (post) will be reduced by at least 33%, e.g. from 6/10 to 4/10.

Pancreas cancer causes pain in 70% of newly diagnosed patients rising to over 80% in advanced cancer patients, and is the most common serious symptom. Pancreas cancer pain is strongly correlated with worsened survival, and relief of pain is correlated with better survival. Pancreas cancer pain is neuropathic in origin and sensation, arising from direct invasion of local tissues. Pancreas cancer pain is relieved by local nerve blocks in about 75% of cases, but the relief is often incomplete, temporary, and the procedure is invasive with some risks. As the cancer grows to involve more nerves, or the nerves regrow, the pain typically comes back. For the 46,420 newly diagnosed pancreas cancer patients and the 39,500 patients who die of it each year, pain is the one constant symptom.

Scrambler Therapy is a novel treatment increasingly supported by clinical experience and multiple trials. The goal of the device is to provide "non-pain" information through the cutaneous nerves to block the effect of pain information. The device is a cutaneous electrical stimulator that creates waveforms simulating 16 different action potentials, then transmits the action potentials via C fibers. The goal is to reset the brain to perceive "non-pain" from areas previously interpreted as painful, similar to spinal cord stimulation. The multiprocessor apparatus directly stimulates the peripheral nerves by the application of surface electrodes on the skin, similar to EKG electrodes, putting the electrodes above and below the site of pain.

Preliminary data on Scrambler therapy in pancreas cancer Scrambler Therapy appears to work on pain based on results from multiple trials. In fact, the first trial was done on patients with abdominal pain from abdominal cancers. In this first trial, 11 cancer patients (3 pancreas, 4 colon, 4 gastric) suffering from drug resistant visceral pain were studied during the patients' first ten treatment sessions. The pain score before the treatment is shown next to the pain score after treatment, for each daily treatment. The electrodes were placed to surround the pain, following the dermatomes, as shown in Figure 2. The active (yellow) electrodes are always paired across the pain with the passive (black) electrode. Pain was quickly and markedly reduced and maintained until death. As then inventor wrote, "During the applications, all the patients reported a very rapid (in the order of a few seconds) disappearance of the perception of pain. All patients responded fully to the protocol and none reported undesirable side effects. Compliance was excellent." Nine of 11 stopped pain drugs within the first 5 applications. "During the reference period, nine out of eleven patients (81.8%) are seen to have stopped requesting painkillers between the second and the fifth treatment session. The remaining two patients (18.2%) considerably reduced the dosage and undertook mild therapy."

To be blunt, no one really believed these results. The magnitude of pain relief was large, with a simple machine using non-invasive therapy. To this day, the trial has not been replicated. But over the next decade, more and more evidence about Scrambler Therapy emerged from different investigators that led the investigators to believe that there was a signal worth exploring for relief in pancreas cancer. In the second trial, 226 patients with neuropathic pain including failed back surgery, brachial plexus neuropathy, and others were treated. Over 80% of patients responded with \> 50% pain relief, 10% responded with pain relief from 25% to 49%, and only 10% had no response (P\<0.0001). Based on these results the FDA approved Scrambler Therapy for cancer pain treatment February 25, 2009. The investigators have recently compiled the published reports of Scrambler Therapy for a review.

4. Study Procedures

Study Design and Treatment Plan The investigators propose a straightforward single arm trial of actual Scrambler Therapy to see if pain can be relieved. This study also serves to get preliminary information for planning future, larger, phase III studies that could compare to celiac plexus block, spinal cord stimulation, or sham treatment. The investigators anticipate completing the study in less than 12 months, with 18 completed subjects having up to 10 treatment sessions each.

Recruitment

1. Patients will be recruited through the Kimmel Cancer Center's outpatient oncology clinics, and the inpatient oncology and palliative care consult services. The palliative care service now sees over 1000 new consultations annually, with about half with cancer, and pancreas cancer pain is one of the most common reasons for consultation.

Treatment Days

Day 1/Treatment Initiation:

1. Treatment should be initiated by turning on the stimulus for the first electrode pair. The intensity of the stimulus is increased until the patient can first feel some sensation associated with one or both of the electrodes. Script: "Tell me when something is felt."
2. Then, over a few seconds, the intensity is increased to what is maximally tolerated. "Tell me when tolerance has been reached." In practice, this has been universally understood.
3. Once the intensity is at its maximum setting, the research therapist will evaluate the level of pain. If the pain level is not decreased, the machine will be reset to zero, the electrodes will be repositioned and the machine will be restarted in the manner described above. If the pain is not resolved with one set of electrodes, a second set will be applied in a similar fashion. Once satisfactory electrode placement and stimulus intensity is determined, therapy is maintained for a total of 30 minutes.
4. If a patient develops pain or a burning sensation with any of the electrodes, then the treatment should be interrupted and the electrode should be evaluated. Considerations include subjective patient intolerance, stimulation of a cutaneous nerve branch, or exacerbation of hyperesthesia or allodynia associated with the neuropathic process. These problems can be addressed by moving one or both of the electrodes farther away from the area of pain. For the electrodes that were moved, the intensity should again be increased and maintained at maximum for 30 minutes as described above.

Days 2-10:

1. Treatment will be administered using the same principles (each day evaluated independently and not necessarily reproducing the electrode arrangements and stimulation parameters of the previous day) for 30 minutes on consecutive days (Monday-Friday for 2 weeks).
2. Up to two or three days may be skipped to allow for weekends and/or holidays, if needed. If the participant presents without any pain, then the treatment will be "held" for that day and this information will be recorded.
3. Treatment does not proceed if the patient does not have pain.

Dose and Application

1. Electrodes are applied on the skin surrounding the pain-affected area.
2. The electrodes are never applied directly on the pain area, unless there is no pain free area. In that case, the electrode will be applied to the most pain

Statistical Considerations Overall This is a single-arm, pilot study to evaluate the effect of Scrambler Therapy for patients with pancreas cancer who have an average daily pain rating of ≥4 out of 10 based on the Modified Brief Pain Index, question #3.

Sample Size and Accrual The investigators are anticipating that the starting pain score on average will be ≥4 based on Virginia Commonwealth (VCU), Hopkins, Italian, and Mayo Clinic data. The investigators are conservatively anticipating that a relative reduction in average pain score by Day 28 will be 33%, a level which is considered minimal clinically important, based on the VCU, Italian, Mayo Clinic, and Walter Reed data. It is anticipated that approximately 90% of the patients will agree to be re-evaluated at Day 28 and have paired ratings available for evaluation. Thus, the study will enroll 20 patients expecting 18 to be evaluable for the primary endpoint. Based on prior studies, the investigators assume that the average pain value at baseline is at least 4 on a 0-10 scale with a standard deviation (SD) of the original pain value expected to fall in the range of 1-1.5 in this patient population.

As such, a conservative estimate of the standard deviation of the change across patients from Day 0 to Day 28 would be approximately up to 2. Using a one-sample paired t test with a sample size of 18 patients, this design will provide at least 80% power to detect a minimum of 33% reduction in average pain score at Day 28 compared to Day 0 with a two-sided type I error of 5%. The table below shows statistical power under different scenarios of a range of baseline pain scores and intra-patient correlation for a 33% relative reduction at Day 28. In the situation when variation of the starting pain score is larger than expected (e.g., SD=2.0), the sample size remains sufficient for this endpoint if the patients have moderate to severe pain to start with (i.e., 5 or above).

Analysis of Primary Endpoint

1. Baseline and change at Day 28 in average daily pain score will be treated as continuous variables and summarized with descriptive statistics. Each will be explored to determine if transformations (e.g. log or square-root) are necessary to achieve normality.
2. Exploratory plots will be created and means will be estimated along with 95% confidence intervals.
3. The investigators will use the paired t-test and Wilcoxon sign rank test as appropriate to determine whether or not the data shows evidence of change from baseline.
4. The primary analysis will include all patients who have received at least one session of treatment; the investigators' experience is that \>90% will complete treatment.
5. A sensitivity analysis may be performed with patients who have completed 10 sessions of treatment, but the investigators anticipate that this highly motivated group will have \>90% completion rates.

Analysis of Secondary Endpoints

1. All of the secondary endpoints will be summarized by item and by type of questionnaire, respectively, using descriptive statistics. A summary score of Brief Pain Inventory (BPI) will also be calculated by adding the total number of points across items.
2. The normality of distributions will be assessed and transformations be made as appropriate. Mean changes will be estimated with 95% confidence intervals. Changes from baseline will be evaluated using paired t tests or Wilcoxon signed rank tests.
3. A repeated measure of analysis of variance (ANOVA) will be used to test if there are any changes over time on pain scores.
4. Adjustment for multiple comparisons will not be made due to the pilot nature of study seeking to generate hypotheses to be tested in future larger randomized trials.

A Pilot Trial of Scrambler Therapy for Pain Associated With Pancreas Cancer

Change in average pain will be evaluated using the Brief Pain Inventory Question 3. This is scored from 0 to 10 with 0 being no pain and 10 being worst pain.

The change in pain will be assessed by the standard Brief Pain Inventory which has 35 items with an overall scoring of 0 to 10. A score of 0 means no pain and a score of 10 means worst pain.

The amount of opioids in milligrams used between day 0 and day 28 will be converted to morphine equivalents to assess any change in the amount of opioid used.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Postmastectomy Pain Syndrome in an Indian Cancer Hospital	NCT03067922	Pain Syndrome Mastectomy Quality of Life	Non interventio...	18 Years - 80 Years	Tata Memorial Centre
Postmastectomy Pain Syndrome in an Indian Cancer Hospital	NCT03067922	Pain Syndrome Mastectomy Quality of Life	Non interventio...	18 Years - 80 Years	Tata Memorial Centre
Muscle Energy Technique Versus Maitland Mobilization on Shoulder Pain and Disability	NCT06010381	Neck Cancer Mobility Limita... Pain Syndrome Shoulder Pain Surgery	Muscle energy t... Maitland mobili... Traditional sho...	25 Years - 70 Years	Cairo University
Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib	NCT04565600	Pain Syndrome	Etoricoxib	18 Years -	Guangdong Provincial People's Hospital
The Impact of Pecs Blocks on Postmastectomy Pain Syndrome	NCT04586751	Pain Syndrome Pain, Postopera... Chronic Pain Breast Cancer Breast Soft Tis... Breast Neoplasm... Breast Cancer F... Breast Pain Anesthesia	Pecs block no Pecs block	20 Years - 85 Years	Aretaieion University Hospital
A Pilot Trial of Scrambler Therapy for Pain Associated With Pancreas Cancer	NCT03707444	Cancer Pancreas Pain Syndrome Cancer Related ...	Scrambler Thera...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Pilot Trial of Scrambler Therapy for Pain Associated With Pancreas Cancer	NCT03707444	Cancer Pancreas Pain Syndrome Cancer Related ...	Scrambler Thera...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Postmastectomy Pain Syndrome in an Indian Cancer Hospital	NCT03067922	Pain Syndrome Mastectomy Quality of Life	Non interventio...	18 Years - 80 Years	Tata Memorial Centre

Spots Global Cancer Trial Database for pain syndrome